Model of Chronic Itch in Aged Mice: Beneficial Effects of Drugs Affecting Descending Modulatory Systems.

Pruritus in the elderly, particularly those cases without skin dryness or other identifiable causes, makes treatment challenging due to the lack of evidence regarding the therapeutic effects of antipruritics. This study proposes an age-related alloknesis mouse model for an evaluation system for such cases, and aimed to investigate the effectiveness and mechanisms of action of several drugs commonly used as antipruritics in Japan, utilizing this model. Mice 69-80 weeks old were used as aged mice, and the level of mechanical alloknesis was counted as the number of scratching behaviours in response to innocuous stimuli. Bepotastine, neurotropin, pregabalin, baricitinib, and abrocitinib were used as antipruritics, and yohimbine and methysergide as inhibitors of the descending inhibitory pathway. The findings suggest that mechanical alloknesis in aged mice is a suitable animal model for assessing pruritus in the elderly without xerosis, and pregabalin, neurotropin, baricitinib, and abrocitinib may be effective antipruritics in the elderly through activating both the noradrenergic and serotonergic descending inhibitory pathways. These findings may be useful for the selection of antipruritics for pruritus in the elderly without skin lesions or dryness.

Effects of Psychological Stress on Spontaneous Itch and Mechanical Alloknesis of Atopic Dermatitis.

Atopic dermatitis (AD), a chronic inflammatory skin disease, manifests as an intractable itch. Psychological stress has been suggested to play a role in the onset and worsening of AD symptoms. However, the pathophysiological relationships between psychological stressors and cutaneous manifestations remain unclear. To elucidate the mechanisms underlying the stress-related exacerbation of itch, we investigated the effects of water stress, restraint stress and repeated social defeat stress on itch-related scratching behaviour, mechanical alloknesis and dermatitis in male NC/Nga mice with AD-like symptoms induced by the repeated application of ointment containing Dermatophagoides farina body. NC/Nga mice with AD-like symptoms were subjected to water stress, restraint stress and repeated social defeat stress, and their scratching behaviour, sensitivity to mechanical stimuli (mechanical alloknesis) and severity of  dermatitis were evaluated. Social defeat stress+ Dermatophagoides farina body-treated mice exposed to stress showed slower improvements in or the exacerbation of AD-like symptoms, including dermatitis and itch. In the mechanical alloknesis assay, the mechanical alloknesis scores of social defeat stress+ Dermatophagoides farina body-treated mice exposed to stress were significantly higher than those of non-exposed social defeat stress+ Dermatophagoides farina body- and social defeat stress-treated mice. These results suggest that psychological stress delays improvements in dermatitis by exacerbating itch hypersensitivity in AD.

Peripheral endomorphins drive mechanical alloknesis under the enzymatic control of CD26/DPPIV.

BACKGROUND: Mechanical alloknesis (or innocuous mechanical stimuli-evoked itch) often occurs in dry skin-based disorders such as atopic dermatitis and psoriasis. However, the molecular and cellular mechanisms underlying mechanical alloknesis remain unclear. We recently reported the involvement of CD26 in the regulation of psoriatic itch. This molecule exhibits dipeptidyl peptidase IV (DPPIV) enzyme activity and exerts its biologic effects by processing various substances, including neuropeptides. OBJECTIVE: The aim of the present study was to investigate the peripheral mechanisms of mechanical alloknesis by using CD26/DPPIV knockout (CD26KO) mice. METHODS: We applied innocuous mechanical stimuli to CD26KO or wild-type mice. The total number of scratching responses was counted as the alloknesis score. Immunohistochemical and behavioral pharmacologic analyses were then performed to examine the physiologic activities of CD26/DPPIV or endomorphins (EMs), endogenous agonists of µ-opioid receptors. RESULTS: Mechanical alloknesis was more frequent in CD26KO mice than in wild-type mice. The alloknesis score in CD26KO mice was significantly reduced by the intradermal administration of recombinant DPPIV or naloxone methiodide, a peripheral µ-opioid receptor antagonist, but not by that of mutant DPPIV without enzyme activity. EMs (EM-1 and EM-2), selective ligands for µ-opioid receptors, are substrates for DPPIV. Immunohistochemically, EMs were located in keratinocytes, fibroblasts, and peripheral sensory nerves. Behavioral analyses revealed that EMs preferentially provoked mechanical alloknesis over chemical itch. DPPIV-digested forms of EMs did not induce mechanical alloknesis. CONCLUSION: The present results suggest that EMs induce mechanical alloknesis at the periphery under the enzymatic control of CD26/DPPIV.

Visceral fat area is a better indicator of surgical outcomes after laparoscopic gastrectomy for cancer than the body mass index: a propensity score-matched analysis.

BACKGROUND: The number of overweight gastric cancer patients who are undergoing laparoscopic gastrectomy (LG) has increased in Japan. However, the relationship between obesity and surgical outcomes of LG remains unclear. Therefore, this study aimed to evaluate the effect of visceral fat area (VFA) on surgical outcomes of LG for gastric cancer compared to the body mass index (BMI). METHODS: This study was a retrospective, cohort study that included 587 patients who underwent LG in our institution between January 2015 and December 2019. The patients were divided into two groups according to VFA (< 100 cm2 and ≥ 100 cm2) and BMI (< 25 kg/m2 and ≥ 25 kg/m2) values, respectively. Surgical outcomes and postoperative complications were compared between the low and high groups for each VFA and BMI value. Propensity score matching was used to minimize potential selection bias. RESULTS: After propensity score matching, 144 pairs of patients in the VFA group and 82 pairs of patients in the BMI group were extracted. Operative time (p = 0.003), intraoperative blood loss (p = 0.0006), and CRP levels on postoperative day 1 (p = 0.002) and on postoperative day 3 (p = 0.004) were significantly higher in the high-VFA group than in the low-VFA group. However, these surgical outcomes were not significantly different between the high-BMI and low-BMI groups. There was no strong correlation between VFA and BMI (R2 = 0.64). There were no significant differences in postoperative complications between the high and low groups for both VFA and BMI values. On multivariate analysis, high VFA was an independent predictor of operative time, but it was not significantly associated with the incidence of postoperative complications. CONCLUSION: VFA is a better indicator of longer operative time than BMI. However, increased VFA did not affect postoperative complications.

Advantages of Laparoscopic Surgery for Gastric Cancer in Elderly Patients Aged Over 80 Years: A Propensity Score Matching Analysis.

BACKGROUND: The short- and long-term efficacy of laparoscopic surgery for elderly patients with gastric cancer has not been evaluated. We aimed to use propensity score matching to clarify the efficacy of laparoscopic gastrectomy (LG) for elderly patients with gastric cancer aged ≥80 years. METHODS: We retrospectively collected data from 159 consecutive patients with gastric cancer aged ≥80 years who underwent gastrectomy with curative intent at our institution between 2004 and 2015. Propensity score matching was applied to compare the open gastrectomy (OG) and LG. Short- and long-term outcomes were evaluated between the propensity-matched groups. RESULTS: Patients' backgrounds and surgical factors were similar in both groups except for blood loss. The median time to first flatus was significantly shorter in the LG group than in the OG group (P = 0.002). The postoperative hospital stay was significantly shorter in the LG group (P = 0.014). The complication rate of Clavien-Dindo grade III or higher was significantly lower in the LG group (3% vs. 23%, P = 0.023). The 5-year overall survival and 5-year disease-specific survival rates were better in the LG group than in the OG group, but the differences were not significant (45% vs. 42% and 67% vs 57%, respectively). CONCLUSION: LG was associated with good short-term outcomes and acceptable oncologic outcomes compared with OG in these propensity-matched patients aged ≥80 years.

T stage and venous invasion are crucial prognostic factors for long-term survival of patients with remnant gastric cancer: a cohort study.

BACKGROUND: The incidence of remnant gastric cancer (RGC) after distal gastrectomy is 1-5%. However, as the survival rate of patients with gastric cancer improves due to early detection and treatment, more patients may develop RGC. There is no consensus on the surgical and postoperative management of RGC, and the clinicopathological characteristics correlated with the long-term outcomes remain unclear. Therefore, we investigated the clinicopathological factors associated with the long-term outcomes of RGC. METHODS: We included 65 consecutive patients who underwent gastrectomy for RGC from January 2000 to December 2015 at the Osaka Medical and Pharmaceutical University Hospital, Japan. The Kaplan-Meier method was used to create survival curves, and differences in survival were compared between the groups (clinical factors, pathological factors, and surgical factors) using the log-rank test. Multivariate analyses using the Cox proportional hazard model were used to identify factors associated with long-term survival. RESULTS: No significant differences were noted in the survival rate based on clinical factors (age, body mass index, diabetes mellitus, hypertension, cardiovascular disease, pulmonary complications, liver disease, diet, history of alcohol drinking, and history of smoking) or the type of remnant gastrectomy. Significant differences were noted in the survival rate based on pathological factors and surgical characteristics (intraoperative blood loss, operation time, and the number of positive lymph nodes). Multivariate analysis revealed that the T stage (hazard ratio, 5.593; 95% confidence interval [CI], 1.183-26.452; p = 0.030) and venous invasion (hazard ratio, 3.351; 95% CI, 1.030-10.903; p = 0.045) were significant independent risk factors for long-term survival in patients who underwent radical resection for RGC. CONCLUSIONS: T stage and venous invasion are important prognostic factors of long-term survival after remnant gastrectomy for RGC and may be keys to managing and identifying therapeutic strategies for improving prognosis in RGC.

The usefulness of intraoperative neurological monitoring for esophageal cancer with double aortic arch; a case report.

BACKGROUND: Double aortic arch (DAA) is a congenital anomaly of the aorta. Esophageal cancer with DAA is rare, and consequently, the appropriate surgical approach has not been standardized. Herein, we report the utilization of intraoperative neurological monitoring (IONM) system to preserve the function of the recurrent laryngeal nerve. CASE PRESENTATION: A 79-year-old man with esophageal cancer was diagnosed with DAA incidentally. The descending aorta was located on the right side of the thoracic vertebrae. Safe dissection of the mediastinal lymph nodes was difficult using the right transthoracic approach because of the anatomical abnormalities. During surgery, we used cervical mediastinoscopy combined with the IONM system to preserve the bilateral recurrent laryngeal nerves. Severe complications, including recurrent nerve palsy, were not observed postoperatively. CONCLUSION: IONM may be useful for evaluation of the function of the recurrent laryngeal nerve, and it would be suitable for atypical cases of esophageal cancer.

[A Case of Remnant Gastric Cancer Occurring 12 Years after Surgery That Was Successfully Treated with Radiation Therapy].

A 59-year-old woman had a history of distal gastrectomy and D2 dissection in May 200X for advanced gastric cancer(GC) in the antrum area. The pathological stage was poorly differentiated, T2(SS), N2, H0, P0, CY0, M0, pStage ⅢA. After administration of S-1 for 1 year as adjuvant chemotherapy, the patient underwent surveillance with no recurrence. However, remnant GC was diagnosed in April 200X+12. Considering that there was no indication for curative resection due to severe invasion of the proper hepatic artery, gastrojejunostomy was performed for the anastomotic stenosis. Although the patient was administered 3 courses of S-1 plus oxaliplatin therapy as first-line treatment, partial response was not achieved. Therefore, chemoradiotherapy(CRT)with capecitabine was administered for local tumor control. Complete response was achieved, and the patient underwent surveillance with no recurrence 16 months after the recurrence. There were no serious acute adverse events(AEs)during CRT and late AEs after CRT. The patient was successfully treated with CRT for locally advanced remnant GC. Although there is no standard treatment for locally advanced remnant GC, this case showed the effectiveness of CRT.

Protocol for enhanced recovery after surgery improves short-term outcomes for patients with gastric cancer: a randomized clinical trial.

BACKGROUND: The feasibility of the use of the enhanced recovery after surgery (ERAS) protocol in patients with gastric cancer remains unclear. METHODS: This study was a single-center, prospective randomized trial involving patients with gastric cancer undergoing curative gastrectomy. The primary end point was the length of postoperative hospital stay. Secondary end points were the postoperative complication rate, admission costs, weight loss, and amount of physical activity. RESULTS: From July 2013 to June 2015, we randomized 148 patients into an ERAS protocol group (n = 73) and a conventional protocol group (n = 69); six patients withdrew from the study. The hospital stay was significantly shorter in the ERAS protocol group than in the conventional protocol group (9 days vs 10 days; P = 0.037). The ERAS protocol group had a significantly lower rate of postoperative complications of grade III or higher (4.1% vs 15.4%; P = 0.042) and reduced costs of hospitalization (JPY 1,462,766 vs JPY 1,493,930; P = 0.045). The ratio of body weight to preoperative weight at 1 week and 1 month after the operation was higher in the ERAS protocol group (0.962 vs 0.957, P = 0.020, and 0.951 vs 0.937, P = 0.021, respectively). The ERAS protocol group recorded more physical activity in the first week after surgery. CONCLUSIONS: The ERAS protocol is safe and efficient, and seems to improve the postoperative course of patients with gastric cancer.

[Local excision of T1b anal canal cancer - a case report].

We performed transanal local excision of anal canal cancer in a 51-year-old man. The tumor was detected as an Isp polyp(7 mm)on the dentate line, by colonofiberscopic examination. Pathological findings indicated adenocarcinoma(T1b). The patient desired preservation of anal function, and hence refused abodominoperineal rectal transection with lymph node dissection. We obtained informed consent for recurrence, and observed the patient rigorously. No recurrence or metastasis has been detected 3 years and 3 months after tumor excision. We propose that transanal local excision might be a treatment option for early stage cancer of the anal canal.

[A case of stage IV rectal cancer successfully resected after chemotherapy (mFOLFOX6 plus panitumumab)].

A 6 6-year-old woman with hematochezia was admitted to our hospital. A colonoscopy detected KRAS wild-type rectal cancer. An abdominal computed tomography (CT) scan revealed a liver metastasis, and invasion to the uterus was suspected. The patient underwent a laparotomy, and intraoperative cytology and peritoneal dissemination proved positive. The tumor had invaded the uterus. We administered chemotherapy consisting of 5-fluorouracil, Leucovorin, and oxaliplatin(mFOL FOX6)plus panitumumab. A CT scan and colonoscopy performed after 10 courses of chemotherapy indicated remarkable tumor regression. An abdominal CT scan did not detect any liver metastases, and we performed a laparoscopic low anterior resection. In the second operation, peritoneal dissemination and washing cytology were negative. The pathological diagnosis of the surgically resected specimen was ypStageII. The patient is recurrence-free 7 months after surgery.

[A case of resection for a huge pancreatic acinar cell carcinoma with tumor thrombus in the portal vein].

A 6 3-year-old man with a huge pancreatic tumor was referred to our hospital. Abdominal computed tomography revealed a heterogeneously enhanced encapsulated mass, 14 cm in diameter, in the pancreas head. The tumor thrombus extended to the bifurcation of the portal vein. The tumor, which had invaded the descending duodenum, was diagnosed as a probable case of acinar cell carcinoma, based on the biopsy results. Prior to resection, we prepared an ileocecal vein-umbilical vein bypass. Initially, we planned to perform a pancreatoduodenectomy, however, a total pancreatectomy had to be performed due to the atrophy of the residual pancreas tail. Since the tumor thrombus was visible, floating up from the portal vein wall at the upper level of pancreas, we dissected the portal vein at this level. The thrombus was extracted after securing the main tract and both (right and left) branches of the portal vein with vessel tape. About 5 cm of portal vein was resected and reconstructed. Since patients who undergo resection of acinar cell carcinoma have a better prognosis and long-term survival is often reported for cases of resected tumor thrombus of the portal vein, it is advisable to resect acinar cell carcinomas even in cases as advanced as reported here.

[A case of advanced gastric cancer successfully treated with trastuzumab, capecitabine, and Cisplatin therapy followed by curative resection].

We report a case of human epidermal growth factor receptor 2(HER2)-positive advanced gastric cancer successfully treated with combination therapy of trastuzumab, capecitabine, and cisplatin, followed by a curative resection. A 23-year-old woman was diagnosed with advanced type 3 gastric cancer, and the clinical findings were T3N0M0, StageIIA. A laparoscopic exploration revealed that it was a CY1 unresectable StageIV cancer. Initially, docetaxel, cisplatin, and S-1 therapy was chosen. However, the patient's HER2 status proved to be positive (IHC 3+), and so trastuzumab, capecitabine and cisplatin therapy was administered. After four cycles, the tumor significantly decreased in size, suggesting a partial response(PR). A further laparoscopic exam showed no apparent dissemination or metastatic cancer cells. We performed a curative resection consisting of a laparoscopic distal gastrectomy and D2 lymphadenectomy. The patient's postoperative course has been uneventful. She has been alive for 4 months and is receiving adjuvant chemotherapy comprising trastuzumab and S-1.

An individual's physique is associated with the length of the reconstruction route via the retrosternal approach.

We hypothesized that an individual's physique is related to reconstruction length, as organs reconstructed via the retrosternal route are curved toward the ventral side. This study aimed to determine factors contributing to the reconstruction length of the retrosternal route. Fifty patients underwent subtotal esophagectomy with esophagogastric reconstruction via the posterior mediastinal route between 2010 and 2014; the esophagus-stomach and posterior mediastinal route lengths were measured to evaluate whether they could be approximated. Forty patients underwent reconstruction via the retrosternal route between 2015 and 2020; the esophagus-stomach and retrosternal route lengths were compared, and contributing factors were analyzed. Each length was measured perioperatively using three-dimensional enhanced computed tomography images. The associated factors obtained included age, sex, height, body weight, body mass index, thickness and height of the thorax, depth of the thoracic inlet space, thoracic curve, left hepatic lobe volume, and the thickness and height of the liver. The length of the esophagus-stomach could approximate that of the posterior mediastinal route [posterior mediastinal-esophagus-stomach; 0.04 (-0.5-0.6) cm, p = 0.77]. Using three-dimensional enhanced computed tomography images, the lengths of the esophagus-stomach and retrosternal routes were comparable, despite variability [retrosternal-esophagus-stomach; 0.72 (-0.1-1.8) cm, p = 0.095]. Analyzing factors associated with the length revealed a positive correlation of body weight, body mass index, and thickness of the thorax with the difference. A higher body mass index (OR = 1.7, 95% CI 1.1-2.8, p = 0.007) was associated with a longer retrosternal route in the multivariate analysis. An individual's physique is associated with the reconstruction length; particularly, the length of the retrosternal route was longer in patients with a high body mass index.

The usefulness of presepsin in the diagnosis of postoperative infectious complications after gastrectomy for gastric cancer: a prospective cohort study.

This prospective study aimed to evaluate presepsin use as a biomarker of on postoperative infectious complications after gastrectomy, compared to C-reactive protein (CRP), white blood cells (WBCs), and neutrophils (Neuts). Overall, 108 patients were enrolled between October 2019 and December 2020. Presepsin, CRP, WBC, and Neut levels were measured preoperatively and on postoperative days (PODs) 1, 3, 5, and 7, using a postoperative morbidity survey. Grade II or higher infectious complications occurred in 18 patients (16.6%). Presepsin levels on all evaluated PODs were significantly higher in the infectious complication group than in the non-complication group (p = 0.002, p < 0.0001, p < 0.0001, and p = 0.025, respectively). The area under the curve (AUC) values were the highest for presepsin on PODs 3 and 7 (0.89 and 0.77, respectively) and similar to that of CRP, with a high value > 0.8 (0.86) on POD 5. For presepsin, the optimal cut-off values were 298 pg/mL (sensitivity, 83.3%; specificity, 83.3%), 278 pg/mL (sensitivity, 83.3%; specificity, 82.2%), and 300 pg/mL (sensitivity, 83.3%; specificity, 82%) on PODs 3, 5, and 7, respectively. Presepsin levels on PODs 3, 5, and 7 after gastrectomy is a more useful biomarker of postoperative infectious complications compared to CRP, WBCs, and Neuts, with a high sensitivity and specificity.

Comparison of the gastric microbiome in Billroth I and Roux-en-Y reconstructions after distal gastrectomy.

The changes in gastric microbiota following reconstruction after gastrectomy have not been reported. This study aimed to compare the gastric microbiota following Billroth I and Roux-en-Y reconstructions after distal gastrectomy. We enrolled 71 gastrectomized patients with gastric cancer; 31 and 40 underwent Billroth I and Roux-en-Y reconstructions, respectively. During upper gastrointestinal endoscopy, gastric fluid was collected immediately before and 6 months after distal gastrectomy. Deoxyribonucleic acid isolated from each sample was evaluated using 16S ribosomal ribonucleic acid metagenomic analysis. Analysis revealed that the gastric microbiota's species richness (expressed as the alpha diversity) was significantly lower after than before distal gastrectomy (operational taxonomic units, p = 0.001; Shannon index, p = 0.03). The interindividual diversity (beta diversity) was significantly different before and after distal gastrectomy (unweighted UniFrac distances, p = 0.04; weighted UniFrac distances, p = 0.001; Bray-Curtis, p = 0.001). Alpha and beta diversity were not significantly different between Billroth I and Roux-en-Y reconstructions (observed operational taxonomic units, p = 0.58; Shannon index, p = 0.95; unweighted UniFrac distances, p = 0.65; weighted UniFrac distances, p = 0.67; Bray-Curtis, p = 0.63). Our study demonstrated significant differences in gastric microbiota diversity, composition, and community before and after distal gastrectomy but no difference between Billroth I and Roux-en-Y reconstruction after distal gastrectomy.

A successful case of varix of the left gastroepiploic vein preoperatively diagnosed by 3D-CT angiography and resected by laparoscopy: A case report.

INTRODUCTION: Gastric varices can be present in up to 20% of patients with portal hypertension. However, a varix of the left gastroepiploic vein (LGV) is extremely rare. Surgery is required if bleeding occurs; thus, precise diagnosis is crucial. We present a successful case of preoperative diagnosis intraabdominal varix of the LGV using three-dimensional-computed tomography angiography (3D-CTA) followed by laparoscopic resection. This is the first report of a case with variant LGV. Our study demonstrates the efficacies of 3D-CTA and laparoscopic surgery for the diagnosis and safe resection of the intraabdominal varix, respectively. PATIENT CONCERNS: A 74-year-old woman was referred to our department with a tumor in the abdominal cavity. On physical examination, no lumps were palpable in the upper abdomen. DIAGNOSIS: The enhanced CT was revealed that the tumor was not enhanced in the early phase, but in the equilibrium phase. Moreover, 3D-CTA clearly revealed that the tumor was being supplied by the LGV. Thus, it was diagnosed as a variant of the LGV. INTERVENTIONS: Surgical resection was performed laparoscopically as per the guidance of preoperative 3D-CTA findings. During surgery, a dark tumor was found along the gastroepiploic vessels, supplied by the LGV. The tumor was resected safely based on the preoperative information. OUTCOMES: Histopathological examination of the tumor showed accumulation of various vessels, but no malignant cells. Therefore, we made a final diagnosis of the tumor as an LGV varix. For follow-up, an annual CT examination was performed and after 3 years postoperation, no recurrence was observed. CONCLUSIONS: In the present case, we have achieved a successful preoperative diagnosis using 3D-CTA, and resection was safely accomplished using laparoscopy guided by preoperative anatomical information. This is the first report of an LGV variant. Appropriate management is crucial because bleeding is a catastrophic event. Therefore, imaging procedures such as 3D-CTA for diagnosis, followed by safe resection by laparoscopic surgery, are effective tools for the treatment of epiploic vein varices.

Esophago-bronchial fistula treated by the Over-The-Scope-Clipping (OTSC) system with argon beam electrocoagulation: A case report.

RATIONALE: An esophago-bronchial fistula is one of the rare postoperative complications of esophageal cancer. There are various medical treatments, including suturing, endoscopic clip, and fibrin glue. However, these treatments often lead to unsatisfactory results, causing physicians to opt for surgical alternatives. The Over-The-Scope-Clipping (OTSC) system offers an alternative method for fistula closure. It can capture a large amount of tissue and is able to compress the lesion until it has fully healed. However, data indicating the efficacy of OTSC for esophago-bronchial fistula are limited. PATIENT CONCERNS: A 64-year-old man presented with an esophago-bronchial fistula after surgery for esophageal cancer. We chose to use a stent as the first line of treatment, but the fistula did not close. DIAGNOSES: Intractable esophago-bronchial fistula associated with esophageal surgery. INTERVENTIONS AND OUTCOMES: On the 94th postoperative day, fistula closure with OTSC was performed, and no leakage of the contrast agent was observed during fluoroscopy. We also attempted to close the fistula by combining OTSC and argon plasma coagulation (APC) to burn off the scar tissue from around the fistula. The fistula gradually shrank after a total of 4 rounds of OTSC, and closure of the fistula was achieved on the 185th postoperative day. There were no adverse events during the treatment of this case. LESSONS: We demonstrate that OTSC is useful in the management of esophago-bronchial fistulas, and may become a standard procedure for the endoscopic treatment of esophago-bronchial fistulas, replacing the use of stents, clips, or glue.

Calcium-Inducible MAPK/AP-1 Signaling Drives Semaphorin 3A Expression in Normal Human Epidermal Keratinocytes.

Epidermal keratinocytes are primarily involved in the expression of semaphorin (Sema) 3A, which is involved in the regulation of cutaneous innervation. However, the mechanisms underlying the intracellular signaling of Sema3A expression in keratinocytes remain unknown. We herein investigated the signaling mechanisms for the induction of Sema3A expression in normal human epidermal keratinocytes (NHEKs). Sema3A expression is transiently increased in calcium-stimulated NHEKs, whereas it is markedly decreased in terminally differentiated NHEKs. Sema3A mRNA is mainly localized in the stratum basale and stratum suprabasale of the epidermis. We cloned the 5'-flanking region of the Sema3A gene and identified a critical region for Sema3A promoter activity within -134 base pairs of the start codon. We found transcription factor binding sites, including that for activator protein (AP)-1, in this region. Sema3A expression was increased by the co-overexpression of JunB and Fra-2 in the presence of 0.1 or 1.4 mM calcium. The calcium-mediated transient upregulation of Sema3A expression was significantly suppressed by mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK) 1/2 or AP-1 inhibitors. These results demonstrate that the calcium-mediated transient upregulation of Sema3A in NHEKs is involved in the MEK/ERK and AP-1 signaling axis. Therefore, Sema3A mRNA may be expressed in the lower epidermis under controlled conditions by calcium via the MAPK-AP-1 axis.

Protein-losing enteropathy secondary to nonocclusive mesenteric ischemia: A case report.

RATIONALE: Nonocclusive mesenteric ischemia (NOMI) is a life-threatening disorder; prompt diagnosis is vital. Surgical treatment is often required, but some cases can be treated conservatively. We herein report an extremely rare case wherein protein-losing enteropathy (PLE) developed after conservative treatment of NOMI. PATIENT CONCERNS: The patient was a 66-year-old man. He underwent laparoscopic super low anterior resection and temporary ileostomy for sigmoid colon cancer and rectum cancer. During the postoperative course, he developed ileus. Subsequently, he developed shock. On examination, the possibility of NOMI could not be denied, but intestinal necrosis was absent. Conservative treatment was initiated. His general condition improved, but the ileus persisted. Therefore, we performed a stoma closure. Ten days after stoma closure, he developed continuous unexplained diarrhea. The serum albumin and total protein levels were low. The symptoms improved after administration of an antidiarrheal drug, but the root cause was yet untreated. DIAGNOSIS: The patient's alpha-1 antitrypsin clearance was increased. A CT scan revealed an enhanced hypertrophied wall of the short segment of the small intestine, and 99m Tc-labeled human serum albumin scintigraphy revealed protein leakage into the thickened wall of the small intestine. We arrived at a definitive diagnosis of PLE secondary to NOMI. INTERVENTIONS: Partial resection of the affected small intestine was performed. OUTCOMES: The patient recovered uneventfully and was discharged on the 30th postoperative day. LESSONS: NOMI has a high mortality rate, often requiring intestinal resection immediately after onset. To our knowledge, there is no report of PLE developing after conservative treatment, as in our case. Further study of cases is necessary to determine the reversibility of the condition, which will influence the therapeutic plan. We herein present an extremely rare case of PLE after conservative treatment for NOMI. The possibility of PLE also needs to be considered when hypoalbuminemia occurs after conservative treatment of NOMI.